The melanocortin system plays a key role in the regulation of food intake and energy homeostasis. Genetic mutations that result in the absence of or aberrant expression of these hormones have an obese phenotype. The mechanism of action of melanocortins and how such signals engage central systems related to food intake remain unclear. Preliminary data in our laboratory indicates that the hypothalamic melanocortin system engages the mitogen activated protein kinase (MAPK) signal transduction pathway. This application proposes to further study this activation and to use it as a tool to investigate the neural pathways that are engaged by melanocortins. Specifically, the experiments within this proposal were designed to 1) examine the activation of MAPK by melanocortins, 2) to determine the source of input to neurons with activated MAPK after melanocortin treatment, 3) to determine the neurochemical phenotype of neurons with activated MAPK after melanocortin treatment, and 4) to examine changes in gene expression that result from melanocortin treatment that may mediate the effects of melanocortins on food intake and energy homeostasis.